Candidate's Plans/Training: The candidate plans a career as an independent clinical investigator focusing on patient-oriented research related to pulmonary vascular disease. Training will include formal epidemiological course work in clinical research and closely mentored completion of the research protocol. Environment: The Center for Clinical Epidemiology and Biostatistics (CCEB) will provide formal coursework and structured mentoring. The CCEB, Pulmonary Vascular Disease Program, and General Clinical Research Center at the University of Pennsylvania Medical Center will provide research support. Research: Primary pulmonary hypertension (idiopathic) and secondary pulmonary hypertension (associated with portal hypertension, anorectic use, HIV, scleroderma, and other collagen vascular diseases) cause substantial morbidity and mortality. Although there are available therapies and interventions, they may be costly and risky in themselves. In addition, targeting therapy at the mechanism of morbidity and mortality and distinguishing highrisk patients have been suboptimal. There is evidence that certain vasoactive substances may play an important role in the disease process of pulmonary arterial hypertension. Studies have documented elevated levels of endothelin, natriuretic peptides, and norepinephine in patients with this disease. It is well known that these neurohormones play important mechanistic and predictive roles in left-sided heart failure. Similarly, there is much potential for these neurohormone levels in determining 1) the mechanism of disease and 2) the prognosis in pulmonary arterial hypertension. We propose an investigation of patients with pulmonary arterial hypertension to examine whether levels of these biomarkers at baseline and at six month follow-up are associated with right-sided heart failure and cardiovascular death. We will formulate prediction rules using neurohormone levels and clinical variables to improve prognostication and management in this disease.